RESUMEN
RNA-binding motif protein 5 (RBM5) acts as a tumor suppressor in various human cancers and presents with several important characteristics, such as the potentiation of apoptosis, inhibition of the cell cycle, and alternative splicing of Fas and caspase-2 precursor mRNA. However, its role in bladder urothelial carcinoma (BUC) remains unknown. In this study, we found that RBM5 expression was significantly down-regulated in BUC tissues when compared with the adjacent nontumor tissues. The down-regulation of RBM5 activates ß-catenin, which binds to the T-cell factor/lymphocyte enhancer factor element of the miR-432-5p promoter and elevates the expression of miR-432-5p in bladder cancer cells. The up-regulated miR-432-5p directly targets 3'-UTR and depresses RBM5 expression. Thus, RBM5-miR-432-5p-ß-catenin forms a feedback loop in regulating bladder cancer cell apoptosis. Our findings provide evidence that the regulatory feedback loop among RBM5, miR-432-5p, and Wnt-ß-catenin is responsible for the progress of bladder cancer cells.-Zhang, Y.-P., Liu, K.-L., Wang, Y.-X., Yang, Z., Han, Z.-W., Lu, B.-S., Qi, J.-C., Yin, Y.-W., Teng, Z.-H., Chang, X.-L., Li, J.-D., Xin, H., Li, W. Down-regulated RBM5 inhibits bladder cancer cell apoptosis by initiating an miR-432-5p/ß-catenin feedback loop.
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Apoptosis , Proteínas de Ciclo Celular/genética , Proteínas de Unión al ADN/genética , Retroalimentación Fisiológica , MicroARNs/metabolismo , Proteínas de Unión al ARN/genética , Proteínas Supresoras de Tumor/genética , Neoplasias de la Vejiga Urinaria/metabolismo , beta Catenina/metabolismo , Animales , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Proteínas de Unión al ADN/metabolismo , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/genética , Proteínas de Unión al ARN/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Neoplasias de la Vejiga Urinaria/genética , Urotelio/metabolismo , beta Catenina/genéticaRESUMEN
The radiation intensity of observed auroras in the far-ultraviolet (FUV) band varies dramatically with location for aerospace applications, requiring a photon counting imaging apparatus with a wide dynamic range. However, combining high spatial resolution imaging with high event rates is technically challenging. We developed an FUV photon counting imaging system for aurora observation. Our system mainly consists of a microchannel plate (MCP) stack readout using a wedge strip anode (WSA) with charge induction and high-speed electronics, such as a charge sensitive amplifier (CSA) and pulse shaper. Moreover, we constructed an anode readout model and a time response model for readout circuits to investigate the counting error in high counting rate applications. This system supports global rates of 500 kilo counts, 0.610 dark counts s-1 cm-2 at an ambient temperature of 300 K and 111 µm spatial resolution at 400 kilo counts s-1 (kcps). We demonstrate an obvious photon count loss at incident intensities close to the counting capacity of the system. To preserve image quality, the response time should be improved and some noise performance may be sacrificed. Finally, we also describe the correlation between counting rate and imaging resolution, which further guides the design of space observation instruments.
RESUMEN
Splicing factor 3B subunit 4 (SF3B4) plays important functional roles not only in pre-mRNA splicing, but also in the regulation of transcription, translation, and cell signaling, and its dysregulation contributes to various diseases including Nager syndrome and tumorigenesis. However, the role of SF3B4 and underlying mechanisms in clear cell renal cell carcinoma (ccRCC) remain obscure. In the present study, we found that the expression of SF3B4 was significantly elevated in ccRCC tissues and negatively correlated with the overall survival of ccRCC patients. Upregulation of SF3B4 promotes migration and invasion of ccRCC cells in vitro and in vivo. The promoting effect of SF3B4 on cell migration and invasion is mediated by Twist1, a key transcription factor to mediate EMT. Interestingly, SF3B4, a component of the pre-mRNA spliceosome, is able to promote KLF16 expression by facilitating the transport of KLF16 mRNA into the cytoplasm. Mechanistically, SF3B4 promotes the export of KLF16 mRNA from the nucleus to the cytoplasm and thus enhances KLF16 expression, and in turn elevated KLF16 directly binds to the Twist1 promoter to activate its transcription, leading to EMT and ccRCC progression. Our findings provide evidence that the SF3B4-KLF16-Twist1 axis plays important functional roles in the development and progression of ccRCC, and manipulating this pathway may be a novel therapeutic target for the treatment of ccRCC.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/metabolismo , Precursores del ARN/metabolismo , ARN Mensajero/genética , Citoplasma/metabolismo , Línea Celular Tumoral , Neoplasias Renales/metabolismo , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteína 1 Relacionada con Twist/genética , Proteína 1 Relacionada con Twist/metabolismo , Factores de Transcripción de Tipo Kruppel/metabolismo , Factores de Empalme de ARN/genética , Factores de Empalme de ARN/metabolismoRESUMEN
Cyclin-dependent kinases (CDKs) regulate cell cycle progression and the transcription of a number of genes, including lipid metabolism-related genes, and aberrant lipid metabolism is involved in prostate carcinogenesis. Previous studies have shown that CDK13 expression is upregulated and fatty acid synthesis is increased in prostate cancer (PCa). However, the molecular mechanisms linking CDK13 upregulation and aberrant lipid metabolism in PCa cells remain largely unknown. Here, we showed that upregulation of CDK13 in PCa cells increases the fatty acyl chains and lipid classes, leading to lipid deposition in the cells, which is positively correlated with the expression of acetyl-CoA carboxylase (ACC1), the first rate-limiting enzyme in fatty acid synthesis. Gain- and loss-of-function studies showed that ACC1 mediates CDK13-induced lipid accumulation and PCa progression by enhancing lipid synthesis. Mechanistically, CDK13 interacts with RNA-methyltransferase NSUN5 to promote its phosphorylation at Ser327. In turn, phosphorylated NSUN5 catalyzes the m5C modification of ACC1 mRNA, and then the m5C-modified ACC1 mRNA binds to ALYREF to enhance its stability and nuclear export, thereby contributing to an increase in ACC1 expression and lipid deposition in PCa cells. Overall, our results disclose a novel function of CDK13 in regulating the ACC1 expression and identify a previously unrecognized CDK13/NSUN5/ACC1 pathway that mediates fatty acid synthesis and lipid accumulation in PCa cells, and targeting this newly identified pathway may be a novel therapeutic option for the treatment of PCa.
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Acetil-CoA Carboxilasa , Neoplasias de la Próstata , Humanos , Masculino , Acetil-CoA Carboxilasa/genética , Acetil-CoA Carboxilasa/metabolismo , Proteína Quinasa CDC2 , Ácidos Grasos , Lípidos , Metiltransferasas , Proteínas Musculares , Próstata/metabolismo , Neoplasias de la Próstata/genética , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
Background: Neutrophil extracellular traps (NETs) are web-like structures formed by neutrophils, and their main function is antimicrobial defense. Moreover, NETs have numerous roles in the pathogenesis and progression of cancers. However, the potential roles of NET-related genes in renal cell carcinoma remain unclear. In this study, we comprehensively investigated the NETs patterns and their relationships with tumor environment (TME), clinicopathological features, prognosis, and prediction of therapeutic benefits in the clear cell renal cell carcinoma (ccRCC) cohort. Methods: We obtained the gene expression profiles, clinical characteristics, and somatic mutations of patients with ccRCC from The Cancer Genome Atlas database (TCGA), Gene Expression Omnibus (GEO), and ArrayExpress datasets, respectively. ConsensusCluster was performed to identify the NET clusters. The tumor environment scores were evaluated by the "ESTIMATE," "CIBERSORT," and ssGSEA methods. The differential analysis was performed by the "limma" R package. The NET-scores were constructed based on the differentially expressed genes (DEGs) among the three cluster patterns using the ssGSEA method. The roles of NET scores in the prediction of immunotherapy were investigated by Immunophenoscores (TCIA database) and validated in two independent cohorts (GSE135222 and IMvigor210). The prediction of targeted drug benefits was implemented using the "pRRophetic" and Gene Set Cancer Analysis (GSCA) datasets. Real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) was performed to identify the reliability of the core genes' expression in kidney cancer cells. Results: Three NET-related clusters were identified in the ccRCC cohort. The patients in Cluster A had more metabolism-associated pathways and better overall survival outcomes, whereas the patients in Cluster C had more immune-related pathways, a higher immune score, and a poorer prognosis than those in Cluster B. Based on the DEGs among different subtypes, patients with ccRCC were divided into two gene clusters. These gene clusters demonstrated significantly different immune statuses and clinical features. The NET scores were calculated based on the ten core genes by the Gene Set Variation Analysis (GSVA) package and then divided ccRCC patients into two risk groups. We observed that high NET scores were associated with favorable survival outcomes, which were validated in the E-MTAB-1980 dataset. Moreover, the NET scores were significantly associated with immune cell infiltration, targeted drug response, and immunotherapy benefits. Subsequently, we explored the expression profiles, methylation, mutation, and survival prediction of the 10 core genes in TCGA-KIRC. Though all of them were associated with survival information, only four out of the 10 core genes were differentially expressed genes in tumor samples compared to normal tissues. Finally, RT-PCR showed that MAP7, SLC16A12, and SLC27A2 decreased, while SLC3A1 increased, in cancer cells. Conclusion: NETs play significant roles in the tumor immune microenvironment of ccRCC. Identifying NET clusters and scores could enhance our understanding of the heterogeneity of ccRCC, thus providing novel insights for precise individual treatment.
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The solar X-ray and Extreme Ultraviolet Imager (X-EUVI), developed by the Changchun Institute of Optics, Fine Mechanics and Physics, Chinese Academy of Sciences (CIOMP), is the first space-based solar X-ray and Extreme ultraviolet (EUV) imager of China loaded on the Fengyun-3E (FY-3E) satellite supported by the China Meteorological Administration (CMA) for solar observation. Since started work on July 11, 2021, X-EUVI has obtained many solar images. The instrument employs an innovative dual-band design to monitor a much larger temperature range on the Sun, which covers 0.6-8.0 nm in the X-ray region with six channels and 19.5 nm in the EUV region. X-EUVI has a field of view of 42', an angular resolution of 2.5â³ per pixel in the EUV band and an angular resolution of 4.1â³ per pixel in the X-ray band. The instrument also includes an X-ray and EUV irradiance sensor (X-EUVS) with the same bands as its imaging optics, which measures the solar irradiance and regularly calibrates the solar images. The radiometric calibration of X-EUVS on the ground has been completed, with a calibration accuracy of 12%. X-EUVI is loaded on the FY-3E satellite and rotates relative to the Sun at a uniform rate. Flat-field calibration is conducted by utilizing successive rotation solar images. The agreement between preliminarily processed X-EUVI images and SDO/AIA and Hinode/XRT images indicates that X-EUVI and the data processing algorithm operate properly and that the data from X-EUVI can be applied to the space weather forecast system of CMA and scientific investigations on solar activity.
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Prostate cancer (PCa) is a frequently occurring malignancy in males, and epithelial mesenchymal transition (EMT) plays a critical role in PCa metastasis. Thus, developing biomarkers inhibiting EMT may provide significance for treatment of PCa. Hence, the aim of the current study was to investigate the mechanism by which FBP1 gene silencing influences PCa cell EMT, invasion and metastasis by mediating the MAPK pathway. PCa cell lines exhibiting the highest FBP1 expression were selected and treated with plasmids of siRNA-FBP1 sequence 1 and 2, pcDNA3.1-Flag-FBP1 (over-expression plasmid of FBP1), U0126 (an inhibitor of the ERK signaling pathway) and PD98059 (an inhibitor of the MEK signaling pathway). Cell proliferation, migration and invasion were detected by MTT assay, wound healing assay and Transwell assay, respectively. The mRNA and protein expression of related factors of EMT and MAPK signaling were determined by RT-qPCR and western blot analysis, respectively. Xenograft tumor growth after inoculation of DU145 cells was regularly analyzed in the nude mice. The positive expression of EMT markers was determined by immunohistochemistry. DU-145 and PC-3 cells displaying the highest FBP1 expression were selected for further analysis. The PCa cells treated with siRNA-FBP1 exhibited increased proliferation, migration rate and invasion, in addition to facilitated xenograft tumor growth. Notably, siRNA-FBP1 was identified to accelerate PCa cell EMT by elevating the expression of Vimentin and N-cadherin while diminishing E-cadherin expression via activation of the MAPK signaling pathway. The aforementioned results were reversed in PCa cells treated by pcDNA3.1-Flag-FBP1. Evidence has been provided in this study that FBP1 gene silencing activates the MAPK pathway, which ultimately promotes cell EMT, invasion and metastasis in PCa.
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Transición Epitelial-Mesenquimal/genética , Sistema de Señalización de MAP Quinasas/genética , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Animales , Cadherinas/genética , Cadherinas/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Fructosa-Bifosfatasa/genética , Fructosa-Bifosfatasa/metabolismo , Regulación Neoplásica de la Expresión Génica/genética , Técnicas de Silenciamiento del Gen , Silenciador del Gen , Humanos , Quinasas Quinasa Quinasa PAM/antagonistas & inhibidores , Quinasas Quinasa Quinasa PAM/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Invasividad Neoplásica/genética , Metástasis de la Neoplasia , Fosforilación , Neoplasias de la Próstata/enzimología , Neoplasias de la Próstata/genética , ARN Interferente Pequeño , Trasplante Heterólogo , Vimentina/genética , Vimentina/metabolismoRESUMEN
The newly launched Fengyun-3D (FY-3D) satellite carried a wide-field auroral imager (WAI) that was developed by Changchun Institute of Optics, Fine Mechanics and Physics, Chinese Academy of Sciences (CIOMP), which will provide a large field of view (FOV), high spatial resolution, and broadband ultraviolet images of the aurora and the ionosphere by imaging the N2 LBH bands of emissions. The WAI consists of two identical cameras, each with an FOV of 68° in the along-track direction and 10° in the cross-track direction. The two cameras are tilted relative to each other to cover a fan-shaped field of size 130° × 10°. Each camera consists of an unobstructed four-mirror anastigmatic optical system, a BaF2 filter, and a photon-counting imaging detector. The spatial resolution of WAI is ~10 km at the nadir point at a reference height of 110 km above the Earth's surface. The sensitivity is >0.01 counts s-1 Rayleigh-1 pixel-1 (140-180 nm) for both cameras, which is sufficient for mapping the boundaries and the fine structures of the auroral oval during storms/substorms. Based on the tests and calibrations that were conducted prior to launch, the data processing algorithm includes photon signal decoding, geometric distortion correction, photometric correction, flat-field correction, line-of-sight projection and correction, and normalization between the two cameras. Preliminarily processed images are compared with DMSP SSUSI images. The agreement between the images that were captured by two instruments demonstrates that the WAI and the data processing algorithm operate normally and can provide high-quality scientific data for future studies on auroral dynamics.